Pre-miR-149 rs71428439 polymorphism is associated with increased cancer risk and AKT1/cyclinD1 signaling in hepatocellular carcinoma.

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most common lethal malignancies in the world, and the current knowledge on the molecular and genetic basis of HCC is still limited. Previous study has shown miR-149 plays a tumor suppressive role in HCC, here we aimed to investigate the association between rs71428439 polymorphism, which located in the pre-miR-149, and the risk of HCC in a Chinese Han population. A total of 177 HCC patients and 103 healthy controls were genotyped, by a multivariate logistic regression, we found that individuals with GG genotype have significantly higher risk of HCC (adjusted OR=3.397, 95% CI=1.565-7.375, P=0.002) compared with those with AA genotype, similar results were also observed in recessive model (adjusted OR=2.563, 95% CI=1.300-5.054, P=0.007) and dominant model (adjusted OR=2.074, 95% CI=1.147-3.752, P=0.016). We further observed that tumor tissues in patients with GG genotype expressed lower level of miR-149 compared with those with AA or AG genotype, and consequently, AKT1, a pre-validated miR-149 target in vitro, was found to have higher expression level in tumors with GG genotype. In summary, our data indicated that rs71428439 may be a genetic risk factor of HCC in the Chinese Han population, and its mechanism possibly involves downregulated miR-149 expression and upregulated AKT1 expression.